There is a compelling need for new approaches to prevention and control of periodontitis. A vaccine may be feasible, especially in highly susceptible groups and individuals. The humoral immune response can be protective and can alter the course of periodontal destruction. This multidisciplinary Program Project proposes to continue to obtain answers to fundamental questions about the immune response to antigens of periodontopathic bacteria, and to work toward development of a vaccine. We will more completely characterize the nonhuman primate model in which we successfully suppressed the progress of periodontitis by immunization. Using the same vaccine and a similar protocol as previously, we will add 28 animals to the 20 already studied. We will induce periodontitis by ligature placement as before, but extend the protocol to evaluate the consequence of ligature removal and superinfection. We will characterize the subgingival flora at baseline and monitor not only Porphyromonas gingivalis but also several species of putative pathogens throughout the study. Clinical manifestations of periodontitis will be recorded and alveolar bone status assessed by digital subtraction radiography. Serum, gingival fluid, and saliva antibody titers and serum antibody avidities for antigens of P. gingivalis will be monitored, and related to disease outcome. We will complete identification and characterization of major cell envelope antigens of A. actinomycetemcomitans, P. gingivalis, and Bacteroides forsythus, and use these antigens to measure IgG titers and subclass in patient and control sera before and after treatment. The protein antigens will be immunologically characterized in rabbits and monkeys to identify those with the greatest potential for future use in a vaccine. The periodontal pathogens have shared antigenic epitopes located in lipopolysaccharide (LPS). We will prepare anti-idiotype vaccines to these epitopes and test their capacity to induce protection. We have evidence that mechanisms other than opsonization are responsible for antibody suppression of alveolar bone resorption. These will be investigated by studying in detail the role of P. gingivalis antigens and serum antibodies on activation and suppression of macrophage and expression of E selectin by endothelial cells. Successful completion of these studies will provide the fundamental information required to develop a vaccine for human periodontitis.